Exercise training is critical for the early prevention and treatment of obesity and diabetes mellitus.However,the mechanism with gut microbiota and fecal metabolites underlying the effects of voluntary wheel running o...Exercise training is critical for the early prevention and treatment of obesity and diabetes mellitus.However,the mechanism with gut microbiota and fecal metabolites underlying the effects of voluntary wheel running on high-fat diet induced abnormal glucose metabolism has not been fully elaborated.C57BL/6 male mice were randomly assigned to 4 groups according to diets(fed with normal chow diet or high-fat diet)and running paradigm(housed in static cage or with voluntary running wheel).An integrative 16S rDNA sequencing and metabolites profiling was synchronously performed to characterize the effects of voluntary wheel running on gut microbiota and metabolites.It showed that voluntary wheel running prevented the detrimental effects of high-fat feeding on glucose metabolism 16S rDNA sequencing showed remarkable changes in Rikenella and Marvinbryantia genera.Metabolic profiling indicated multiple altered metabolites,which were enriched in secondary bile acid biosynthesis signaling.In conclusion,our study indicated that voluntary wheel running significantly improved glucose metabolism and counteracted the deleterious effects of high-fat feeding on body weight and glucose intolerance.We further found that voluntary wheel running could integratively program gut microbiota composition and fecal metabolites changes,and may regulate muricholic acid metabolism and secondary bile acid biosynthesis in high-fat fed mice.展开更多
Forsythia suspensa,belonging to the deciduous shrubs of the Luteaceae family,a traditional Chinese medicine,has effects of alleviating swelling,clearing heat,detoxification and promoting blood circulation.The leaves o...Forsythia suspensa,belonging to the deciduous shrubs of the Luteaceae family,a traditional Chinese medicine,has effects of alleviating swelling,clearing heat,detoxification and promoting blood circulation.The leaves of F.suspensa contain multiple chemical components and have a long history of use in folk medicines and health foods.The purpose of this study was to explore the effects of forsythin extract from F.suspensa leaves on intestinal microbiota and short-chain fatty acid(SCFA)content in rats with obesity induced by a high-fat diet.Forsythin extract in F.suspensa leaves increased the abundance of the intestinal microbiota,ameliorated intestinal microbiota disorders and inhibited the increase in total SCFA content in the intestinal tract in rats with obesity induced by a high-fat diet.These results suggested that forsythin extract in F.suspensa leaves may slow the development of obesity induced by a high-fat diet;thus,its active components and efficacy are worthy of further study.展开更多
BACKGROUND Excessive saturated fat intake compromises the integrity of the intestinal mucosa,leading to low-grade inflammation,impaired mucosal integrity,and increased intestinal permeability,resulting in the migratio...BACKGROUND Excessive saturated fat intake compromises the integrity of the intestinal mucosa,leading to low-grade inflammation,impaired mucosal integrity,and increased intestinal permeability,resulting in the migration of lipopolysaccharide(LPS)to other tissues.AIM To evaluate the chronic effects(at 10 and 16 wk)of a high-fat diet(HFD)(with 50%energy as fat)on the phylogenetic gut microbiota distribution and intestinal barrier structure and protection in C57BL/6 mice.METHODS Forty adult male mice were divided into four nutritional groups,where the letters refer to the type of diet(control and HFD or HF)and the numbers refer to the period(in weeks)of diet administration:Control diet for 10 wk,HFD for 10 wk,control diet for 16 wk,and HFD for 16 wk.After sacrifice,biochemical,molecular,and stereological analyses were performed.RESULTS The HF groups were overweight,had gut dysbiosis,had a progressive decrease in occludin immunostaining,and had increased LPS concentrations.Dietary progression reduced the number of goblet cells per large intestine area and Mucin2 expression in the HF16 group,consistent with a completely disarranged intestinal ultrastructure after 16 wk of HFD intake.CONCLUSION Chronic HFD intake causes overweight,gut dysbiosis,and morphological and functional alterations of the intestinal barrier after 10 or 16 wk.Time-dependent reductions in goblet cell numerical density and mucus production have emerged as targets for countering obesity-driven intestinal damage.展开更多
Background:Type 2 diabetes(T2D)is an adult-onset and obese form of diabetes caused by an interplay between genetic,epigenetic,and environmental components.Here,we have assessed a cohort of 11 genetically different col...Background:Type 2 diabetes(T2D)is an adult-onset and obese form of diabetes caused by an interplay between genetic,epigenetic,and environmental components.Here,we have assessed a cohort of 11 genetically different collaborative cross(CC)mouse lines comprised of both sexes for T2D and obesity developments in response to oral infection and high-fat diet(HFD)challenges.Methods:Mice were fed with either the HFD or the standard chow diet(control group)for 12 weeks starting at the age of 8 weeks.At week 5 of the experiment,half of the mice of each diet group were infected with Porphyromonas gingivalis and Fusobacterium nucleatum bacteria strains.Throughout the 12-week experimental period,body weight(BW)was recorded biweekly,and intraperitoneal glucose tolerance tests were performed at weeks 6 and 12 of the experiment to evaluate the glucose tolerance status of mice.Results:Statistical analysis has shown the significance of phenotypic variations between the CC lines,which have different genetic backgrounds and sex effects in different experimental groups.The heritability of the studied phenotypes was estimated and ranged between 0.45 and 0.85.We applied machine learning methods to make an early call for T2D and its prognosis.The results showed that classification with random forest could reach the highest accuracy classification(ACC=0.91)when all the attributes were used.Conclusion:Using sex,diet,infection status,initial BW,and area under the curve(AUC)at week 6,we could classify the final phenotypes/outcomes at the end stage of the experiment(at 12 weeks).展开更多
Gut dysbiosis is associated with several pathological processes.Previous study showed that regular exercise can protect against dysmetabolism in high-fat diet(HFD)fed mice through butyrate-SESN2 pathway,and SESN2 abla...Gut dysbiosis is associated with several pathological processes.Previous study showed that regular exercise can protect against dysmetabolism in high-fat diet(HFD)fed mice through butyrate-SESN2 pathway,and SESN2 ablation weakened the protective effects of exercise.Here,we investigated whether SESN2-defi ciency suppresses the exercise response to microbiota composition and subsequently reduces the benefi ts of exercise on dysmetabolism induced by HFD.Wild type(WT)and SESN2^(-/-)mice were assigned to fi ve-groups,fed with either normal chow or HFD and with or without exercise training for 15-week.Fecal microbiota composition and function were assessed by 16S rRNA sequencing.The sequencing results showed that SESN2^(-/-)mice displayed differed microbiome profile from WT mice.Exercise enriched the microflora diversity and increased the benefi cial microbial species in WT mice,and SESN2 ablation weakened the benefi cial effects of exercise on microbial resilience following HFD consumption.Moreover,network analysis revealed that exercise increased correlation density and clustering of operational taxonomic units in WT mice only.KEGG demonstrated that some dominant metabolism-related enzymes and modules increased in SESN2^(-/-)mice.Our results indicated that the effects of exercise on metabolism are associated with the perturbations of gut microbiota composition and function,suggesting that SESN2 contributes to maintain metabolic homeostasis.展开更多
Objective Endothelial dysfunction is one candidate for triggering neointima formation after arteriovenous grafts(AVGs),but the factors mediating this process are unclear.The purpose of this study was to investigate th...Objective Endothelial dysfunction is one candidate for triggering neointima formation after arteriovenous grafts(AVGs),but the factors mediating this process are unclear.The purpose of this study was to investigate the role of endoplasmic reticulum stress(ERS)-induced endothelial dysfunction in neointima formation following AVGs in high-fat diet(HFD)mice.Methods CCAAT-enhancer-binding protein-homologous protein(CHOP)knockout(KO)mice were created.Mice were fed with HFD to produce HFD model.AVGs model were applied in the groups of WT ND,WT HFD,and CHOP KO HFD.Human umbilical vein endothelial cells(HUVECs)were cultured with oxidized low density lipoprotein(ox-LDL)(40 mg/L)for the indicated time lengths(0,6,12,24 h).ERS inhibitor tauroursodeoxycholic acid(TUDCA)was used to block ERS.Immunohistochemical staining was used to observe the changes of ICAM1.Changes of ERS were detected by real-time RT-PCR.Protein expression levels and ERS activation were detected by Western blotting.Endothellial cell function was determined by endothelial permeability assay and transendothelial migration assay.Results HFD increased neointima formation in AVGs associated with endothelial dysfunction.At the same time,ERS was increased in endothelial cells(ECs)after AVGs in mice consuming the HFD.In vitro,ox-LDL was found to stimulate ERS,increase the permeability of the EC monolayer,and cause endothelial dysfunction.Blocking ERS with TUDCA or CHOP siRNA reversed the EC dysfunction caused by ox-LDL.In vivo,knockout of CHOP(CHOP KO)protected the function of ECs and decreased neointima formation after AVGs in HFD mice.Conclusion Inhibiting ERS in ECs could improve the function of AVGs.展开更多
Flaxseed oil(FSO)rich in n-3 polyunsaturated fatty acids(PUFAs)can protect against obesity and insulin resistance,but the underlying mechanism is unknown.An integrative multiomics of the microbiome and targeted metab ...Flaxseed oil(FSO)rich in n-3 polyunsaturated fatty acids(PUFAs)can protect against obesity and insulin resistance,but the underlying mechanism is unknown.An integrative multiomics of the microbiome and targeted metab olomics approach was performed to investigate the possible pathway for flaxseed oil supplementation on reducing serum total cholesterol,triglyceride and epididymal adipose in high-fat diet mice.FSO ameliorated the gut microbial dysbiosis by increasing the community diversity and the abundance of Clostridiales and Ruminococcaceae.These effects were associated with the regulation of bile acid(BAs)in the feces.FSO reduced the concentrations of conjugated BAs,such as cholic acid,tauro-α-murocholic acid,and tauro-ursodesoxycholic acid in feces,which in turn inhibit the intestinal farnesoid X receptor(FXR)-fibroblast growth factor(FGF)15 signaling pathway.Further analysis revealed that FSO activated FXR in the liver and regulated downstream gene expression(SHP,SREBP-1c,and CPT-1a),which promoted lipolysis and inhibited lipogenesis.The results of this study suggest that FSO modulates serum lipid concentrations by regulating the gut microbiota,FXR-FGF15 signaling and BA metabolism.展开更多
Objective:To study the preventive effect of fucoidan on non-alcoholic fatty liver disease induced by high fat diet.Methods:The experimental mice were randomly divided into three groups:control group,high-fat diet grou...Objective:To study the preventive effect of fucoidan on non-alcoholic fatty liver disease induced by high fat diet.Methods:The experimental mice were randomly divided into three groups:control group,high-fat diet group and fucoidan intervention group.The control group was fed a standard diet,and the other two groups were fed a high-fat diet.The control group and the high-fat diet group were given normal saline intragastric administration every day,and the intervention group was given intragastric administration of fucoidan polysaccharide solution at a dose of 100 mg∙kg^(-1)∙d^(-1) once a day for continuous intervention for 12 weeks.After the last intragastric administration for 12 h,the body weight and liver weight of each group of mice were measured,and the liver index was calculated.The contents of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC)and triglyceride(TG)in liver tissues of mice in each group were detected by biochemical kit.Hematoxylin-eosin staining(HE)was used to compare the pathological morphological changes of liver tissue in each group.The contents of inflammatory factor interleukin-6(IL-6),tumor necrosis factor(TNF-α)and oxidative stress index malondialdehyde(MDA),and the activities of glutathione peroxidase(GSH-Px)and superoxide dismutase(SOD)in liver tissues of mice in each group were determined.Results:Compared with the control group,the body weight and liver index of mice receiving high fat diet increased significantly(P<0.01).In addition,the contents of TG,TC,AST and ALT in liver tissue of high-fat diet group were significantly increased compared with that of control group(P<0.01).The liver tissue of mice in the high-fat diet group also showed significant pathological changes,accompanied by increased expression of inflammatory factors and a significant increase in oxidative stress response.However,compared with the mice in the high-fat diet group,the above indexes were significantly improved in the liver tissue of the mice treated with fucoidan(P<0.01).Conclusion:Fucoidan can inhibit liver lipid deposition,liver inflammation and oxidative stress induced by high fat diet.展开更多
[Objectives]To determine the improvement effect of vinegar soaked licorice on liver fibrosis induced by carbon tetrachloride(CCl_(4))combined with high-fat diet in rats.[Methods]Subcutaneous injection of 40%-60%CCl_(4...[Objectives]To determine the improvement effect of vinegar soaked licorice on liver fibrosis induced by carbon tetrachloride(CCl_(4))combined with high-fat diet in rats.[Methods]Subcutaneous injection of 40%-60%CCl_(4)olive oil solution(0.3 mL/100 g)combined with a high-fat diet was used for 5 weeks to establish the rat model with liver fibrosis.After the modeling,the rats were divided into a low dose(0.8 g/kg),a medium dose(2.5 g/kg),a high dose(5 g/kg)group,a colchicine(1.5 mg/kg)positive group,and a vinegar group(2 mL/kg).The serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels in the rats were measured automatically.The serum hyaluronic acid(HA)was detected by radioimmunoassay,and the serum laminin(LN)and procollagen type III peptide(PIIIP)levels were measured by enzyme-linked immunoassay.Liver histopathological morphological changes were observed by HE and Masson staining,and expressions of cytochrome CYP2E1 and transcription factor Nrf2 were detected by immunohistochemistry.[Results]The rat liver fibrosis model was established successfully at the 6~(th)week.Compared with the model group,the levels of ALT,AST,HA,LA,PIIIP,CYP2E1 and Nrf2 of all the examined indexes in the dosing group were decreased(P<0.05).As shown in the pictures of liver pathological tissue sections,the liver fibrosis was significantly alleviated in the positive group and the 3 administration groups.[Conclusions]Vinegar soaked licorice can significantly improve the liver fibrosis induced by carbon tetrachloride combined with high-fat diet in rats,and the effect of the high-dose group was similar to that of the positive group.展开更多
[Objectives]This study was conducted to investigate the effects of Polygonatum odoratum polysaccharide(POP)on organ relative weights and reproductive hormone levels in male rats fed a high-fat diet.[Methods]Thirty hea...[Objectives]This study was conducted to investigate the effects of Polygonatum odoratum polysaccharide(POP)on organ relative weights and reproductive hormone levels in male rats fed a high-fat diet.[Methods]Thirty healthy male Sprague-Dawley(SD)rats were randomly divided into two groups according to their body weight:10 in normal control group(Group NC,n=10)and 20 in experimental group(n=20).The rats in experimental group were fed a high-fat diet for eight weeks before they were further randomly divided into two groups:high fat group(Group HF)and high fat+400 mg/(kg·d)POP group(Group HF+POP).In Group HF+POP,the rats were administered with POP for another six weeks,before their blood plasma was collected,and the relative weights of their testis and epididymis were calculated.The plasma levels of testosterone(T),estrogen(E2),follicle-stimulating hormone(FSH),cortisol(C)and luteinizing hormone(LH)were measured by radioimmunoassay,and the plasma levels of sex hormone-binding globulin(SHBG)and insulin-like growth factor-1(IGF-1)were determined by enzyme-linked immunosorbent assay.[Results]Compared with Group HF,POP could effectively inhibit rat obesity caused by high-fat diets,increase the relative weights of their testis and epididymis,plasma levels of LH,E2,FSH,T,SHBG and IGF-1,and reduce the plasma level of E2.[Conclusions]Polygonatum odoratum polysaccharide(POP)is able to effectively regulate the level of reproductive hormones in high-fat diet fed rats,and helps to protect their reproductive function.展开更多
[Objectives]This study was conducted to explore the effects of Polygonatum sibiricum polysaccharide(PSP)on chronic intestinal inflammation caused by high-fat diet.[Methods]Thirty five male healthy SD rats were randoml...[Objectives]This study was conducted to explore the effects of Polygonatum sibiricum polysaccharide(PSP)on chronic intestinal inflammation caused by high-fat diet.[Methods]Thirty five male healthy SD rats were randomly divided into a normal control group(NC,normal diet,n=10)and a high-fat diet group(HF,high-fat diet,n=25).After 8 weeks,an obesity model was established.The HF group was randomly divided into an HF group and a PSP treatment group[PSP,300 mg/(kg·d)].After 6 weeks of intervention with PSP,rat serum was collected,and the spleen and thymus were stripped,and weighed.Serum IgG,IgM,LPS and IL-1βand IL-6 contents were detected by ELISA,and HE staining was adopted to observe the pathological changes of the colon tissue.[Results]PSP reduced the level of LPS caused by high-fat diet and the levels of inflammatory factors IL-6 and TNF-α,increased the indexes of the thymus and spleen serving as immune organs,increased IgG and IgM contents,and alleviated pathological damage to the colon tissue caused by high-fat diet.[Conclusions]This study provides a theoretical basis and experimental basis for the development of drugs for treating metabolic diseases such as obesity and inflammation.展开更多
[Objectives]This study was conducted to investigate the effects of Polygonatum sibiricum polysaccharide(PSP)on antioxidant function in high-fat diet obese rats.[Methods]Thirty five healthy male SD rats were selected t...[Objectives]This study was conducted to investigate the effects of Polygonatum sibiricum polysaccharide(PSP)on antioxidant function in high-fat diet obese rats.[Methods]Thirty five healthy male SD rats were selected to establish an obesity model after feeding a high-fat for 8 weeks.They were then randomly divided into a normal group(NC),a high-fat diet group(HF),and an HF+P.sibiricum polysaccharide group[HF+PSP,300 mg/(kg·d)].After 6 weeks of PSP intervention,the serum and liver of rats were collected,and the activity of aspartate transaminase(AST)and alanine aminotransferase(ALT)in serum,the enzyme activity of superoxide dismutase(SOD),catalase(CAT)and glutathione peroxidase(GSH-Px)and malondialdehyde(MDA)in liver tissue were measured.The pathological changes of liver tissue were observed by HE staining.[Results]Compared with the HF group,PSP could effectively inhibit obesity caused by high-fat diet.It reduced body weight and serum AST and ALT levels,increased the contents of T-SOD,CAT and GSH-Px in the liver,and inhibited the accumulation of MDA content,thereby reducing damage to liver cells caused by a high-fat diet.It indicated that PSP could effectively inhibit obesity in high-fat diet rats and enhance their antioxidant capacity.[Conclusions]This study provides a reference for the study of the antioxidant capacity of PSP.展开更多
Polygonatum sibiricum is a traditional medicinal and dietary plant of the family Liliaceae. The main functional macromolecules of P. sibiricum are polysaccharides, which function in antioxidation and regulating immuni...Polygonatum sibiricum is a traditional medicinal and dietary plant of the family Liliaceae. The main functional macromolecules of P. sibiricum are polysaccharides, which function in antioxidation and regulating immunity. Previous studies have shown that insulin resistance(IR), oxidative stress, and inflammation are important factors in the induction of lipid metabolic diseases such as obesity. Therefore, in this study, we established a high-fat diet-induced rat model of obesity and nonalcoholic fatty liver disease(NAFLD) to explore the potential protective effect of P. sibiricum polysaccharides(PSPs) and the mechanisms behind it. After 4 weeks of high-fat diet feeding to induce obesity, the rats were treated with different doses of PSP solution or distilled water for 6 weeks. Compared with untreated obese rats, PSP-treated obese rats showed a decrease in body weight, serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels, hepatic aspartate aminotransferase and alanine aminotransferase activity, hepatic malondialdehyde content, and hepatic levels of the pro-inflammatory factors tumor necrosis factor-α, interleukin-1β, and interleukin-6, as well as increased serum high-density lipoprotein cholesterol levels and hepatic superoxide dismutase, catalase, and glutathione peroxidase activity. Pathological analysis and immunoblotting of the liver tissues indicated that mechanistically, PSPs reduced obesity and NAFLD in rats by upregulating insulin receptor expression, increasing adenosine monophosphate-activated protein kinase phosphorylation, and downregulating sterol regulatory element-binding protein 2 and low-density lipoprotein receptor expression, thus promoting lipid metabolism, decreasing body weight, and reducing inflammation and oxidative stress caused by lipid accumulation. Based on these results, PSPs may have the potential to reduce obesity and NAFLD associated with a high-fat diet.展开更多
Background: Host genetic background and sex, play central roles in defining the pathogenesis of type 2 diabetes(T2 D), obesity and infectious diseases. Our previous studies demonstrated the utilization of genetically ...Background: Host genetic background and sex, play central roles in defining the pathogenesis of type 2 diabetes(T2 D), obesity and infectious diseases. Our previous studies demonstrated the utilization of genetically highly diverse inbred mouse lines, namely collaborative cross(CC), for dissecting host susceptibility for the development of T2 D and obesity, showing significant variations following high-fat(42% fat) diet(HFD). Here, we aimed to assessing the host genetic background and sex effects on T2 D and obesity development in response to oral-mixed bacterial infection and HFD using the CC lines.Materials and Methods: Study cohort consists of 97 mice from 2 CC lines(both sexes), maintained on either HFD or Standard diet(CHD) for 12 weeks. At week 5 a group of mice from each diet were infected with Porphyromonas gingivalis(Pg) and Fusobacterium nucleatum(Fn) bacteria(control groups without infection). Body weight(BW) and glucose tolerance ability were assessed at the end time point of the experiment.Results: The CC lines varied(P <.05) at their BW gain and glucose tolerance ability(with sex effect) in response to diets and/or infection, showing opposite responses despite sharing the same environmental conditions. The combination of diet and infection enhances BW accumulation for IL1912, while restraints it for IL72. As for glucose tolerance ability, only females(both lines) were deteriorated in response to infection.Conclusions: This study emphasizes the power of the CC mouse population for the characterization of host genetic makeup for defining the susceptibility of the individual to development of obesity and/or impaired glucose tolerance.展开更多
This study aimed to investigate the microRNA expression profile and the characteristics of lipid metabolism in the livers of rats undergoing a high-fat diet.Fifty male Sprague-Dawley(SD)rats were divided into a standa...This study aimed to investigate the microRNA expression profile and the characteristics of lipid metabolism in the livers of rats undergoing a high-fat diet.Fifty male Sprague-Dawley(SD)rats were divided into a standard chow group(C group,N=10)and a high-fat diet group(H group,N=40).After 12 weeks,the rat body weight,body length,fat mass,and serum lipid concentration were measured.The expression profile of microRNAs and the gene and protein expression levels involved in lipid metabolism in rat liver were detected.Body fat and serum lipid concentrations were all significantly higher in the H group than those in the C group(p<0.05 or p<0.01).The expression of 10 microRNAs showed significant differences in the liver(p<0.05).In particular,the let-7 family expression levels significantly increased(p<0.05)in the H group compared with those in the C group.Compared with the C group,the high-fat diet resulted in low FAS,CPT1A,and ApoAI mRNA expression levels(p<0.05 or p<0.01)and high PPARαand FAT/CD36 mRNA expression levels in the H group rat liver(p<0.01).Meanwhile,the protein PPARα,FAS,CPT1A,FAT/CD36,and ApoAI expression levels were all significantly lower in the H group than those in the C group(p<0.05 or p<0.01).In conclusion,the high-fat diet increased the body fat and serum lipid levels and altered the 10 microRNA expression levels in the liver.The high-fat diet may affect hepatic carbohydrate metabolism and increase ectopic fat accumulation through let-7 family overexpression.The high-fat diet for 12 weeks decreased lipid metabolism level in the liver,thereby decreasing fatty acid synthesis,oxidation,and transport by down-regulating the PPARα,FAS,CPT1A,FAT/CD36,and ApoAI protein levels.展开更多
Background:Multimorbidity of intestinal cancer(IC),type 2 diabetes(T2D)and obesity is a complex set of diseases,affected by environmental and genetic risk factors.High-fat diet(HFD)and oral bacterial infection play im...Background:Multimorbidity of intestinal cancer(IC),type 2 diabetes(T2D)and obesity is a complex set of diseases,affected by environmental and genetic risk factors.High-fat diet(HFD)and oral bacterial infection play important roles in the etiology of these diseases through inflammation and various biological mechanisms.Methods:To study the complexity of this multimorbidity,we used the collaborative cross(CC)mouse genetics reference population.We aimed to study the multimorbidity of IC,T2D,and obesity using CC lines,measuring their responses to HFD and oral bacterial infection.The study used 63 mice of both sexes generated from two CC lines(IL557 and IL711).For 12 weeks,experimental mice were maintained on specific dietary regimes combined with co-infection with oral bacteria Porphyromonas gingivalis and Fusobacterium nucleatum,while control groups were not infected.Body weight(BW)and results of a intraperitoneal glucose tolerance test(IPGTT)were recorded at the end of 12 weeks,after which length and size of the intestines were assessed for polyp counts.Results:Polyp counts ranged between 2 and 10 per CC line.The combination of HFD and infection significantly reduced(P<.01)the colon polyp size of IL557 females to 2.5 cm 2,compared to the other groups.Comparing BW gain,IL557 males on HFD gained 18 g,while the females gained 10 g under the same conditions and showed the highest area under curve(AUC)values of 40000-45000(min mg/dL)in the IPGTT.Conclusion:The results show that mice from different genetic backgrounds respond differently to a high fat diet and oral infection in terms of polyp development and glucose tolerance,and this effect is gender related.展开更多
Purpose:Monoacylglycerol O-acyltransferase 1(MGAT1)is reported to play a key role in the development of diet-induced nonalcoholic fatty liver disease(NAFLD).Thus,this study investigated the effect of exercise on suppr...Purpose:Monoacylglycerol O-acyltransferase 1(MGAT1)is reported to play a key role in the development of diet-induced nonalcoholic fatty liver disease(NAFLD).Thus,this study investigated the effect of exercise on suppression of the MGAT1 pathway in NAFLD tissue of high-fat diet(HFD)-induced obese rats.Methods:Male Sprague-Dawley rats were fed an HFD containing 45%fat for 6 weeks.Upon confirmation that NAFLD had been induced in the obese animals,they were divided into HFD-fed groups provided with exercise(HFD+EXE)or without exercise(HFD)and a group given dietary adjustment(DA)only,for a further 6 weeks of intervention treatment.The 6-week regular moderate aerobic exercise consisted of an accommodation phase with increasing exercise.Lipid accumulation in the liver tissue was determined by Oil Red O staining.The MGAT1 and liver lipogenic gene mRNA levels were measured by qPCR,and their protein levels by western blot assay.Results:Oil Red O staining showed that NAFLD was successfully induced by HFD-fed.The gene expression of MGAT1 was significantly lower in HFD+EXE than HFD.However,there was no significant difference between HFD+EXE and DA.The protein expression of MGAT1 was significantly lower in HFD+EXE than both HFD and DA.Messenger RNA and protein expression of other lipogenic genes were not different among groups.These data indicate that exercise suppresses MGAT1 pathway regardless of HFD feeding;in part,this effect could be greater than DA.Conclusion:Our data suggest that exercise can improve NAFLD,which is probably due to suppression of MGAT1 pathway.展开更多
BACKGROUND The mechanisms underlying diabetes remission after duodenal-jejunal bypass(DJB) remain elusive. In DJB surgery, the duodenum is excluded. However, the duodenum has emerged as an important regulator of gluco...BACKGROUND The mechanisms underlying diabetes remission after duodenal-jejunal bypass(DJB) remain elusive. In DJB surgery, the duodenum is excluded. However, the duodenum has emerged as an important regulator of glucose homeostasis, and elevated duodenal SIRT1 leads to improved hepatic insulin sensitivity. After DJB, bile acids(BAs) in the duodenum are not mixed and diluted by the ingested food. And activation of BA receptors promotes SIRT1 expression in many tissues. We hypothesized that BA-mediated upregulation of SIRT1 may contribute to diabetic control after DJB.AIM To investigate the surgical effects of DJB on duodenal SIRT1 expression and uncover the potential crosslinks between BAs and SIRT1.METHODS Twenty diabetic rats were randomly allocated to the sham(n = 10) and DJB(n = 10) groups. Body weight, food intake, fasting blood glucose(FBG), serum and intraduodenal total BA(TBA) levels were measured accordingly. Oral glucose tolerance test(OGTT) and intraperitoneal pyruvate tolerance test(ip PTT) were performed to evaluate the effects of surgeries on systemic glucose disposal and hepatic gluconeogenesis. The key genes of BA signaling pathway in the duodenal mucosa, including farnesoid X receptor(FXR), small heterodimer partner(SHP), and Takeda G-protein-coupled receptor 5(TGR5) were evaluated by real-time quantitative polymerase chain reaction 8 wk postoperatively. The duodenal SIRT1, AMPK, and phosphorylated AMPK(p-AMPK) levels were evaluated by western blotting. Rat small intestine epithelial IEC-6 cells were treated with GW4064 and INT-777 to verify the effects of BAs on SIRT1 expression in enterocytes.RESULTS The DJB group exhibited body weight and food intake comparable to those of the sham group at all postoperative time points. The FBG level and area under the curve for the OGTT and ip PTT were significantly lower in the DJB group. The DJB group exhibited higher fasting and postprandial serum TBA levels than the sham group at both 2 and 8 wk postoperatively. At 8 wk after surgery, the DJB group showed higher intraluminal TBA concentration, upregulated m RNA expression of FXR and SHP, and elevated protein expression of SIRT1 and p-AMPK in the descending and horizontal segments of the duodenum. Activation of FXR and TGR5 receptors by GW4064 and INT-777 increased the m RNA and protein expression of SIRT1 and promoted the phosphorylation of AMPK in IEC-6 cells.CONCLUSION DJB elevates intraduodenal BA levels and activates the duodenal BA signaling pathway, which may upregulate duodenal SIRT1 and further contribute to improved glucose homeostasis after DJB.展开更多
Objective Epidemiology studies indicate that green tea polyphenols(GTP)perform a protective effect on cardiovascular diseases,but the underlying mechanisms are complex.The present study aimed to investigate the effect...Objective Epidemiology studies indicate that green tea polyphenols(GTP)perform a protective effect on cardiovascular diseases,but the underlying mechanisms are complex.The present study aimed to investigate the effect of GTP on high-fat diets(HFD)induced-early vascular aging.Methods Six-week young adult Wistar rats were fed with standard chow or HFD in the presence and absence of GTP(200 mg/kg body weight)for 18 weeks.In vitro experiment,human umbilical vascular endothelial cells(HUVECs)were treated with palmitic acid(PA)and GTP.Results The results showed that GTP alleviated the disorganized arterial wall and the increased intima-media thickness induced by HFD.In addition,the vascular oxidative injury was suppressed following GTP treatment.Furthermore,GTP elevated the ratio of LC3-II/LC3-I and suppressed expression of p62/SQSTM1,and restored SIRT3 expression in the aorta of HFD rats.Consistently,in cultured HUVECs,GTP inhibited cell senescence indicated by SA-β-gal and promoted endothelial autophagy compared with the PA treatment group.The activity of SIRT3 was specifically inhibited by 3-TYP,and the protective effect of GTP was consequently abolished.Conclusion The findings indicated that GTP protected against early vascular senescence in young HFD rats via ameliorating oxidative injury and promoting autophagy which was partially regulated by the SIRT3 pathway.展开更多
Excess caloric intake increases the amount of adipose tissue and contributes to metabolic disorders in disrupted metabolic homeostasis.This study aimed to investigate the anti-obesity effects of ginseng and the altern...Excess caloric intake increases the amount of adipose tissue and contributes to metabolic disorders in disrupted metabolic homeostasis.This study aimed to investigate the anti-obesity effects of ginseng and the alternation of gut microbiota composition in high-fat diet(HFD)-induced obesity.The results showed that HFD treatment influenced body weight gain,adipose tissue accumulation and biochemical parameter changes.Compared to the HFD group,ginseng supplementation of HFD-fed mice decreased body weight,adipose tissue mass,total cholesterol(T-CHO)and high-density lipoprotein(HDL)/low-density lipoprotein(LDL)ratio.To analysis the alterations of gut microbiota,ginseng in dietary supplements decreased Firmicutes abundance and increased Bacteroidetes abundance.Taken together,these findings suggest ginseng may modulate the energy storage and alter gut microbiota composition.展开更多
基金sponsored by National Natural Science Foundation of China (81800703 and 81970701)Beijing Nova Program (Z201100006820117 and 20220484181)+7 种基金Beijing Municipal Natural Science Foundation (7184252 and 7214258)the Fundamental Research Funds for the Central Universitiesthe Fundamental Research Funds for the Central Universities (BMU2021MX013)Peking University Clinical Scientist Training Program (BMU2023PYJH022)China Endocrine and Metabolism Young Scientific Talent Research Project (2022-N-02-01)Peking University Medicine Seed Fund for Interdisciplinary ResearchChina Diabetes Young Scientific Talent Research ProjectBethune-Merck Diabetes Research Fund of Bethune Charitable Foundation (G2018030)。
文摘Exercise training is critical for the early prevention and treatment of obesity and diabetes mellitus.However,the mechanism with gut microbiota and fecal metabolites underlying the effects of voluntary wheel running on high-fat diet induced abnormal glucose metabolism has not been fully elaborated.C57BL/6 male mice were randomly assigned to 4 groups according to diets(fed with normal chow diet or high-fat diet)and running paradigm(housed in static cage or with voluntary running wheel).An integrative 16S rDNA sequencing and metabolites profiling was synchronously performed to characterize the effects of voluntary wheel running on gut microbiota and metabolites.It showed that voluntary wheel running prevented the detrimental effects of high-fat feeding on glucose metabolism 16S rDNA sequencing showed remarkable changes in Rikenella and Marvinbryantia genera.Metabolic profiling indicated multiple altered metabolites,which were enriched in secondary bile acid biosynthesis signaling.In conclusion,our study indicated that voluntary wheel running significantly improved glucose metabolism and counteracted the deleterious effects of high-fat feeding on body weight and glucose intolerance.We further found that voluntary wheel running could integratively program gut microbiota composition and fecal metabolites changes,and may regulate muricholic acid metabolism and secondary bile acid biosynthesis in high-fat fed mice.
基金funded by grants from the National Key R&D Program of China(2016YFD0500604)。
文摘Forsythia suspensa,belonging to the deciduous shrubs of the Luteaceae family,a traditional Chinese medicine,has effects of alleviating swelling,clearing heat,detoxification and promoting blood circulation.The leaves of F.suspensa contain multiple chemical components and have a long history of use in folk medicines and health foods.The purpose of this study was to explore the effects of forsythin extract from F.suspensa leaves on intestinal microbiota and short-chain fatty acid(SCFA)content in rats with obesity induced by a high-fat diet.Forsythin extract in F.suspensa leaves increased the abundance of the intestinal microbiota,ameliorated intestinal microbiota disorders and inhibited the increase in total SCFA content in the intestinal tract in rats with obesity induced by a high-fat diet.These results suggested that forsythin extract in F.suspensa leaves may slow the development of obesity induced by a high-fat diet;thus,its active components and efficacy are worthy of further study.
文摘BACKGROUND Excessive saturated fat intake compromises the integrity of the intestinal mucosa,leading to low-grade inflammation,impaired mucosal integrity,and increased intestinal permeability,resulting in the migration of lipopolysaccharide(LPS)to other tissues.AIM To evaluate the chronic effects(at 10 and 16 wk)of a high-fat diet(HFD)(with 50%energy as fat)on the phylogenetic gut microbiota distribution and intestinal barrier structure and protection in C57BL/6 mice.METHODS Forty adult male mice were divided into four nutritional groups,where the letters refer to the type of diet(control and HFD or HF)and the numbers refer to the period(in weeks)of diet administration:Control diet for 10 wk,HFD for 10 wk,control diet for 16 wk,and HFD for 16 wk.After sacrifice,biochemical,molecular,and stereological analyses were performed.RESULTS The HF groups were overweight,had gut dysbiosis,had a progressive decrease in occludin immunostaining,and had increased LPS concentrations.Dietary progression reduced the number of goblet cells per large intestine area and Mucin2 expression in the HF16 group,consistent with a completely disarranged intestinal ultrastructure after 16 wk of HFD intake.CONCLUSION Chronic HFD intake causes overweight,gut dysbiosis,and morphological and functional alterations of the intestinal barrier after 10 or 16 wk.Time-dependent reductions in goblet cell numerical density and mucus production have emerged as targets for countering obesity-driven intestinal damage.
基金Binational Science Foundation(BSF)grant number 2015077German Israeli Science Foundation(GIF)grant I-63-410.20-2017+1 种基金Israeli Science Foundation(ISF)grant 1085/18core fund from Tel Aviv University。
文摘Background:Type 2 diabetes(T2D)is an adult-onset and obese form of diabetes caused by an interplay between genetic,epigenetic,and environmental components.Here,we have assessed a cohort of 11 genetically different collaborative cross(CC)mouse lines comprised of both sexes for T2D and obesity developments in response to oral infection and high-fat diet(HFD)challenges.Methods:Mice were fed with either the HFD or the standard chow diet(control group)for 12 weeks starting at the age of 8 weeks.At week 5 of the experiment,half of the mice of each diet group were infected with Porphyromonas gingivalis and Fusobacterium nucleatum bacteria strains.Throughout the 12-week experimental period,body weight(BW)was recorded biweekly,and intraperitoneal glucose tolerance tests were performed at weeks 6 and 12 of the experiment to evaluate the glucose tolerance status of mice.Results:Statistical analysis has shown the significance of phenotypic variations between the CC lines,which have different genetic backgrounds and sex effects in different experimental groups.The heritability of the studied phenotypes was estimated and ranged between 0.45 and 0.85.We applied machine learning methods to make an early call for T2D and its prognosis.The results showed that classification with random forest could reach the highest accuracy classification(ACC=0.91)when all the attributes were used.Conclusion:Using sex,diet,infection status,initial BW,and area under the curve(AUC)at week 6,we could classify the final phenotypes/outcomes at the end stage of the experiment(at 12 weeks).
基金supported by grants from the National Natural Science Foundation of China(32171135,31871206,and 31671237).
文摘Gut dysbiosis is associated with several pathological processes.Previous study showed that regular exercise can protect against dysmetabolism in high-fat diet(HFD)fed mice through butyrate-SESN2 pathway,and SESN2 ablation weakened the protective effects of exercise.Here,we investigated whether SESN2-defi ciency suppresses the exercise response to microbiota composition and subsequently reduces the benefi ts of exercise on dysmetabolism induced by HFD.Wild type(WT)and SESN2^(-/-)mice were assigned to fi ve-groups,fed with either normal chow or HFD and with or without exercise training for 15-week.Fecal microbiota composition and function were assessed by 16S rRNA sequencing.The sequencing results showed that SESN2^(-/-)mice displayed differed microbiome profile from WT mice.Exercise enriched the microflora diversity and increased the benefi cial microbial species in WT mice,and SESN2 ablation weakened the benefi cial effects of exercise on microbial resilience following HFD consumption.Moreover,network analysis revealed that exercise increased correlation density and clustering of operational taxonomic units in WT mice only.KEGG demonstrated that some dominant metabolism-related enzymes and modules increased in SESN2^(-/-)mice.Our results indicated that the effects of exercise on metabolism are associated with the perturbations of gut microbiota composition and function,suggesting that SESN2 contributes to maintain metabolic homeostasis.
基金funded by the National Natural Science Foundation of China(No.81770413)Hubei Provincial Natural Science Foundation of China(No.2017CFB669).
文摘Objective Endothelial dysfunction is one candidate for triggering neointima formation after arteriovenous grafts(AVGs),but the factors mediating this process are unclear.The purpose of this study was to investigate the role of endoplasmic reticulum stress(ERS)-induced endothelial dysfunction in neointima formation following AVGs in high-fat diet(HFD)mice.Methods CCAAT-enhancer-binding protein-homologous protein(CHOP)knockout(KO)mice were created.Mice were fed with HFD to produce HFD model.AVGs model were applied in the groups of WT ND,WT HFD,and CHOP KO HFD.Human umbilical vein endothelial cells(HUVECs)were cultured with oxidized low density lipoprotein(ox-LDL)(40 mg/L)for the indicated time lengths(0,6,12,24 h).ERS inhibitor tauroursodeoxycholic acid(TUDCA)was used to block ERS.Immunohistochemical staining was used to observe the changes of ICAM1.Changes of ERS were detected by real-time RT-PCR.Protein expression levels and ERS activation were detected by Western blotting.Endothellial cell function was determined by endothelial permeability assay and transendothelial migration assay.Results HFD increased neointima formation in AVGs associated with endothelial dysfunction.At the same time,ERS was increased in endothelial cells(ECs)after AVGs in mice consuming the HFD.In vitro,ox-LDL was found to stimulate ERS,increase the permeability of the EC monolayer,and cause endothelial dysfunction.Blocking ERS with TUDCA or CHOP siRNA reversed the EC dysfunction caused by ox-LDL.In vivo,knockout of CHOP(CHOP KO)protected the function of ECs and decreased neointima formation after AVGs in HFD mice.Conclusion Inhibiting ERS in ECs could improve the function of AVGs.
基金supported by the Shandong Provincial Key Research and Development program(2019GHZ031)the Taishan Scholar Project(Feng-Hong Huang)+2 种基金the Natural Science Foundation of Hubei Province(2019CFB342)the Central Public-interest Scientific Institution Basal Research Fund for Chinese Academy of Agricultural Sciences(1610172019009)the Earmarked Fund for China Agriculture Research System(CARS-14).
文摘Flaxseed oil(FSO)rich in n-3 polyunsaturated fatty acids(PUFAs)can protect against obesity and insulin resistance,but the underlying mechanism is unknown.An integrative multiomics of the microbiome and targeted metab olomics approach was performed to investigate the possible pathway for flaxseed oil supplementation on reducing serum total cholesterol,triglyceride and epididymal adipose in high-fat diet mice.FSO ameliorated the gut microbial dysbiosis by increasing the community diversity and the abundance of Clostridiales and Ruminococcaceae.These effects were associated with the regulation of bile acid(BAs)in the feces.FSO reduced the concentrations of conjugated BAs,such as cholic acid,tauro-α-murocholic acid,and tauro-ursodesoxycholic acid in feces,which in turn inhibit the intestinal farnesoid X receptor(FXR)-fibroblast growth factor(FGF)15 signaling pathway.Further analysis revealed that FSO activated FXR in the liver and regulated downstream gene expression(SHP,SREBP-1c,and CPT-1a),which promoted lipolysis and inhibited lipogenesis.The results of this study suggest that FSO modulates serum lipid concentrations by regulating the gut microbiota,FXR-FGF15 signaling and BA metabolism.
基金Youth Research Project of Shanghai Health and Family Planning Commission (No.20174Y0201)。
文摘Objective:To study the preventive effect of fucoidan on non-alcoholic fatty liver disease induced by high fat diet.Methods:The experimental mice were randomly divided into three groups:control group,high-fat diet group and fucoidan intervention group.The control group was fed a standard diet,and the other two groups were fed a high-fat diet.The control group and the high-fat diet group were given normal saline intragastric administration every day,and the intervention group was given intragastric administration of fucoidan polysaccharide solution at a dose of 100 mg∙kg^(-1)∙d^(-1) once a day for continuous intervention for 12 weeks.After the last intragastric administration for 12 h,the body weight and liver weight of each group of mice were measured,and the liver index was calculated.The contents of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC)and triglyceride(TG)in liver tissues of mice in each group were detected by biochemical kit.Hematoxylin-eosin staining(HE)was used to compare the pathological morphological changes of liver tissue in each group.The contents of inflammatory factor interleukin-6(IL-6),tumor necrosis factor(TNF-α)and oxidative stress index malondialdehyde(MDA),and the activities of glutathione peroxidase(GSH-Px)and superoxide dismutase(SOD)in liver tissues of mice in each group were determined.Results:Compared with the control group,the body weight and liver index of mice receiving high fat diet increased significantly(P<0.01).In addition,the contents of TG,TC,AST and ALT in liver tissue of high-fat diet group were significantly increased compared with that of control group(P<0.01).The liver tissue of mice in the high-fat diet group also showed significant pathological changes,accompanied by increased expression of inflammatory factors and a significant increase in oxidative stress response.However,compared with the mice in the high-fat diet group,the above indexes were significantly improved in the liver tissue of the mice treated with fucoidan(P<0.01).Conclusion:Fucoidan can inhibit liver lipid deposition,liver inflammation and oxidative stress induced by high fat diet.
基金Supported by Inner Mongolia Mongolian Medicine Standardization Project(MB2019)Study on the Concoction Method of Licorice and Its Process(myxylxkky2019-04)。
文摘[Objectives]To determine the improvement effect of vinegar soaked licorice on liver fibrosis induced by carbon tetrachloride(CCl_(4))combined with high-fat diet in rats.[Methods]Subcutaneous injection of 40%-60%CCl_(4)olive oil solution(0.3 mL/100 g)combined with a high-fat diet was used for 5 weeks to establish the rat model with liver fibrosis.After the modeling,the rats were divided into a low dose(0.8 g/kg),a medium dose(2.5 g/kg),a high dose(5 g/kg)group,a colchicine(1.5 mg/kg)positive group,and a vinegar group(2 mL/kg).The serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels in the rats were measured automatically.The serum hyaluronic acid(HA)was detected by radioimmunoassay,and the serum laminin(LN)and procollagen type III peptide(PIIIP)levels were measured by enzyme-linked immunoassay.Liver histopathological morphological changes were observed by HE and Masson staining,and expressions of cytochrome CYP2E1 and transcription factor Nrf2 were detected by immunohistochemistry.[Results]The rat liver fibrosis model was established successfully at the 6~(th)week.Compared with the model group,the levels of ALT,AST,HA,LA,PIIIP,CYP2E1 and Nrf2 of all the examined indexes in the dosing group were decreased(P<0.05).As shown in the pictures of liver pathological tissue sections,the liver fibrosis was significantly alleviated in the positive group and the 3 administration groups.[Conclusions]Vinegar soaked licorice can significantly improve the liver fibrosis induced by carbon tetrachloride combined with high-fat diet in rats,and the effect of the high-dose group was similar to that of the positive group.
基金Supported by Scientific Research Fund of the Hunan Provincial Education Department of China(19A259)Natural Science Foundation of Hunan Province(2022JJ30312)+2 种基金National Innovation Experiment Program for University Students(201910553013)2020 Innovation Experiment Program for College Students of Hunan University of HumanitiesScience and Technology(2020-17)。
文摘[Objectives]This study was conducted to investigate the effects of Polygonatum odoratum polysaccharide(POP)on organ relative weights and reproductive hormone levels in male rats fed a high-fat diet.[Methods]Thirty healthy male Sprague-Dawley(SD)rats were randomly divided into two groups according to their body weight:10 in normal control group(Group NC,n=10)and 20 in experimental group(n=20).The rats in experimental group were fed a high-fat diet for eight weeks before they were further randomly divided into two groups:high fat group(Group HF)and high fat+400 mg/(kg·d)POP group(Group HF+POP).In Group HF+POP,the rats were administered with POP for another six weeks,before their blood plasma was collected,and the relative weights of their testis and epididymis were calculated.The plasma levels of testosterone(T),estrogen(E2),follicle-stimulating hormone(FSH),cortisol(C)and luteinizing hormone(LH)were measured by radioimmunoassay,and the plasma levels of sex hormone-binding globulin(SHBG)and insulin-like growth factor-1(IGF-1)were determined by enzyme-linked immunosorbent assay.[Results]Compared with Group HF,POP could effectively inhibit rat obesity caused by high-fat diets,increase the relative weights of their testis and epididymis,plasma levels of LH,E2,FSH,T,SHBG and IGF-1,and reduce the plasma level of E2.[Conclusions]Polygonatum odoratum polysaccharide(POP)is able to effectively regulate the level of reproductive hormones in high-fat diet fed rats,and helps to protect their reproductive function.
基金Supported by General Project of Natural Science Foundation of Hunan Province (2022JJ30312)National College Student Research-based Learning and Innovative Experimental Program in 2019 (201910553013)College Student Research-based Learning and Innovative Experimental Program of Hunan University of Humanities,Science and Technology in 2020 (17).
文摘[Objectives]This study was conducted to explore the effects of Polygonatum sibiricum polysaccharide(PSP)on chronic intestinal inflammation caused by high-fat diet.[Methods]Thirty five male healthy SD rats were randomly divided into a normal control group(NC,normal diet,n=10)and a high-fat diet group(HF,high-fat diet,n=25).After 8 weeks,an obesity model was established.The HF group was randomly divided into an HF group and a PSP treatment group[PSP,300 mg/(kg·d)].After 6 weeks of intervention with PSP,rat serum was collected,and the spleen and thymus were stripped,and weighed.Serum IgG,IgM,LPS and IL-1βand IL-6 contents were detected by ELISA,and HE staining was adopted to observe the pathological changes of the colon tissue.[Results]PSP reduced the level of LPS caused by high-fat diet and the levels of inflammatory factors IL-6 and TNF-α,increased the indexes of the thymus and spleen serving as immune organs,increased IgG and IgM contents,and alleviated pathological damage to the colon tissue caused by high-fat diet.[Conclusions]This study provides a theoretical basis and experimental basis for the development of drugs for treating metabolic diseases such as obesity and inflammation.
基金Supported by Key Project of Hunan Provincial Department of Education (19A259)General Project of Natural Science Foundation of Hunan Province (2022JJ30312)+1 种基金National College Student Research-based Learning and Innovative Experimental Program in 2019 (201910553013)College Student Research-based Learning and Innovative Experiment Program of Hunan University of Humanities,Science and Technology in 2023 (10,14).
文摘[Objectives]This study was conducted to investigate the effects of Polygonatum sibiricum polysaccharide(PSP)on antioxidant function in high-fat diet obese rats.[Methods]Thirty five healthy male SD rats were selected to establish an obesity model after feeding a high-fat for 8 weeks.They were then randomly divided into a normal group(NC),a high-fat diet group(HF),and an HF+P.sibiricum polysaccharide group[HF+PSP,300 mg/(kg·d)].After 6 weeks of PSP intervention,the serum and liver of rats were collected,and the activity of aspartate transaminase(AST)and alanine aminotransferase(ALT)in serum,the enzyme activity of superoxide dismutase(SOD),catalase(CAT)and glutathione peroxidase(GSH-Px)and malondialdehyde(MDA)in liver tissue were measured.The pathological changes of liver tissue were observed by HE staining.[Results]Compared with the HF group,PSP could effectively inhibit obesity caused by high-fat diet.It reduced body weight and serum AST and ALT levels,increased the contents of T-SOD,CAT and GSH-Px in the liver,and inhibited the accumulation of MDA content,thereby reducing damage to liver cells caused by a high-fat diet.It indicated that PSP could effectively inhibit obesity in high-fat diet rats and enhance their antioxidant capacity.[Conclusions]This study provides a reference for the study of the antioxidant capacity of PSP.
基金financially supported by the Natural Science Foundation of Hunan Province, China (2019JJ40272)the Scientific Research Foundation of Hunan Provincial Education Department, China (20C1676)the Scientific Research Foundation of Shaoyang College, China (2020HX122)。
文摘Polygonatum sibiricum is a traditional medicinal and dietary plant of the family Liliaceae. The main functional macromolecules of P. sibiricum are polysaccharides, which function in antioxidation and regulating immunity. Previous studies have shown that insulin resistance(IR), oxidative stress, and inflammation are important factors in the induction of lipid metabolic diseases such as obesity. Therefore, in this study, we established a high-fat diet-induced rat model of obesity and nonalcoholic fatty liver disease(NAFLD) to explore the potential protective effect of P. sibiricum polysaccharides(PSPs) and the mechanisms behind it. After 4 weeks of high-fat diet feeding to induce obesity, the rats were treated with different doses of PSP solution or distilled water for 6 weeks. Compared with untreated obese rats, PSP-treated obese rats showed a decrease in body weight, serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels, hepatic aspartate aminotransferase and alanine aminotransferase activity, hepatic malondialdehyde content, and hepatic levels of the pro-inflammatory factors tumor necrosis factor-α, interleukin-1β, and interleukin-6, as well as increased serum high-density lipoprotein cholesterol levels and hepatic superoxide dismutase, catalase, and glutathione peroxidase activity. Pathological analysis and immunoblotting of the liver tissues indicated that mechanistically, PSPs reduced obesity and NAFLD in rats by upregulating insulin receptor expression, increasing adenosine monophosphate-activated protein kinase phosphorylation, and downregulating sterol regulatory element-binding protein 2 and low-density lipoprotein receptor expression, thus promoting lipid metabolism, decreasing body weight, and reducing inflammation and oxidative stress caused by lipid accumulation. Based on these results, PSPs may have the potential to reduce obesity and NAFLD associated with a high-fat diet.
基金Israeli Science Foundation (ISF),Grant/Award Number 1085/18German Israeli Science Foundation (GIF),Grant/Award Number I-63-410.20-2017+1 种基金Binational Science Foundation (BSF),Grant/Award Number 2015077Tel-Aviv University
文摘Background: Host genetic background and sex, play central roles in defining the pathogenesis of type 2 diabetes(T2 D), obesity and infectious diseases. Our previous studies demonstrated the utilization of genetically highly diverse inbred mouse lines, namely collaborative cross(CC), for dissecting host susceptibility for the development of T2 D and obesity, showing significant variations following high-fat(42% fat) diet(HFD). Here, we aimed to assessing the host genetic background and sex effects on T2 D and obesity development in response to oral-mixed bacterial infection and HFD using the CC lines.Materials and Methods: Study cohort consists of 97 mice from 2 CC lines(both sexes), maintained on either HFD or Standard diet(CHD) for 12 weeks. At week 5 a group of mice from each diet were infected with Porphyromonas gingivalis(Pg) and Fusobacterium nucleatum(Fn) bacteria(control groups without infection). Body weight(BW) and glucose tolerance ability were assessed at the end time point of the experiment.Results: The CC lines varied(P <.05) at their BW gain and glucose tolerance ability(with sex effect) in response to diets and/or infection, showing opposite responses despite sharing the same environmental conditions. The combination of diet and infection enhances BW accumulation for IL1912, while restraints it for IL72. As for glucose tolerance ability, only females(both lines) were deteriorated in response to infection.Conclusions: This study emphasizes the power of the CC mouse population for the characterization of host genetic makeup for defining the susceptibility of the individual to development of obesity and/or impaired glucose tolerance.
基金supported by Natural Science Foundation Youth Project of Shandong Province,China(Grant No.ZR2014CQ026 to Dr.Wen Jing)The Science Foundation for the Youth of China Institute of Sport Science,China(Grant No.13-19 to Dr.Ying-li Lu).
文摘This study aimed to investigate the microRNA expression profile and the characteristics of lipid metabolism in the livers of rats undergoing a high-fat diet.Fifty male Sprague-Dawley(SD)rats were divided into a standard chow group(C group,N=10)and a high-fat diet group(H group,N=40).After 12 weeks,the rat body weight,body length,fat mass,and serum lipid concentration were measured.The expression profile of microRNAs and the gene and protein expression levels involved in lipid metabolism in rat liver were detected.Body fat and serum lipid concentrations were all significantly higher in the H group than those in the C group(p<0.05 or p<0.01).The expression of 10 microRNAs showed significant differences in the liver(p<0.05).In particular,the let-7 family expression levels significantly increased(p<0.05)in the H group compared with those in the C group.Compared with the C group,the high-fat diet resulted in low FAS,CPT1A,and ApoAI mRNA expression levels(p<0.05 or p<0.01)and high PPARαand FAT/CD36 mRNA expression levels in the H group rat liver(p<0.01).Meanwhile,the protein PPARα,FAS,CPT1A,FAT/CD36,and ApoAI expression levels were all significantly lower in the H group than those in the C group(p<0.05 or p<0.01).In conclusion,the high-fat diet increased the body fat and serum lipid levels and altered the 10 microRNA expression levels in the liver.The high-fat diet may affect hepatic carbohydrate metabolism and increase ectopic fat accumulation through let-7 family overexpression.The high-fat diet for 12 weeks decreased lipid metabolism level in the liver,thereby decreasing fatty acid synthesis,oxidation,and transport by down-regulating the PPARα,FAS,CPT1A,FAT/CD36,and ApoAI protein levels.
文摘Background:Multimorbidity of intestinal cancer(IC),type 2 diabetes(T2D)and obesity is a complex set of diseases,affected by environmental and genetic risk factors.High-fat diet(HFD)and oral bacterial infection play important roles in the etiology of these diseases through inflammation and various biological mechanisms.Methods:To study the complexity of this multimorbidity,we used the collaborative cross(CC)mouse genetics reference population.We aimed to study the multimorbidity of IC,T2D,and obesity using CC lines,measuring their responses to HFD and oral bacterial infection.The study used 63 mice of both sexes generated from two CC lines(IL557 and IL711).For 12 weeks,experimental mice were maintained on specific dietary regimes combined with co-infection with oral bacteria Porphyromonas gingivalis and Fusobacterium nucleatum,while control groups were not infected.Body weight(BW)and results of a intraperitoneal glucose tolerance test(IPGTT)were recorded at the end of 12 weeks,after which length and size of the intestines were assessed for polyp counts.Results:Polyp counts ranged between 2 and 10 per CC line.The combination of HFD and infection significantly reduced(P<.01)the colon polyp size of IL557 females to 2.5 cm 2,compared to the other groups.Comparing BW gain,IL557 males on HFD gained 18 g,while the females gained 10 g under the same conditions and showed the highest area under curve(AUC)values of 40000-45000(min mg/dL)in the IPGTT.Conclusion:The results show that mice from different genetic backgrounds respond differently to a high fat diet and oral infection in terms of polyp development and glucose tolerance,and this effect is gender related.
文摘Purpose:Monoacylglycerol O-acyltransferase 1(MGAT1)is reported to play a key role in the development of diet-induced nonalcoholic fatty liver disease(NAFLD).Thus,this study investigated the effect of exercise on suppression of the MGAT1 pathway in NAFLD tissue of high-fat diet(HFD)-induced obese rats.Methods:Male Sprague-Dawley rats were fed an HFD containing 45%fat for 6 weeks.Upon confirmation that NAFLD had been induced in the obese animals,they were divided into HFD-fed groups provided with exercise(HFD+EXE)or without exercise(HFD)and a group given dietary adjustment(DA)only,for a further 6 weeks of intervention treatment.The 6-week regular moderate aerobic exercise consisted of an accommodation phase with increasing exercise.Lipid accumulation in the liver tissue was determined by Oil Red O staining.The MGAT1 and liver lipogenic gene mRNA levels were measured by qPCR,and their protein levels by western blot assay.Results:Oil Red O staining showed that NAFLD was successfully induced by HFD-fed.The gene expression of MGAT1 was significantly lower in HFD+EXE than HFD.However,there was no significant difference between HFD+EXE and DA.The protein expression of MGAT1 was significantly lower in HFD+EXE than both HFD and DA.Messenger RNA and protein expression of other lipogenic genes were not different among groups.These data indicate that exercise suppresses MGAT1 pathway regardless of HFD feeding;in part,this effect could be greater than DA.Conclusion:Our data suggest that exercise can improve NAFLD,which is probably due to suppression of MGAT1 pathway.
基金Supported by the National Natural Science Foundation of China,No.81600617,81700708,81702647 and 82100853the Natural Science Foundation of Shandong Province,No.ZR2020MH246,ZR2021LZL003 and ZR2021QH028.
文摘BACKGROUND The mechanisms underlying diabetes remission after duodenal-jejunal bypass(DJB) remain elusive. In DJB surgery, the duodenum is excluded. However, the duodenum has emerged as an important regulator of glucose homeostasis, and elevated duodenal SIRT1 leads to improved hepatic insulin sensitivity. After DJB, bile acids(BAs) in the duodenum are not mixed and diluted by the ingested food. And activation of BA receptors promotes SIRT1 expression in many tissues. We hypothesized that BA-mediated upregulation of SIRT1 may contribute to diabetic control after DJB.AIM To investigate the surgical effects of DJB on duodenal SIRT1 expression and uncover the potential crosslinks between BAs and SIRT1.METHODS Twenty diabetic rats were randomly allocated to the sham(n = 10) and DJB(n = 10) groups. Body weight, food intake, fasting blood glucose(FBG), serum and intraduodenal total BA(TBA) levels were measured accordingly. Oral glucose tolerance test(OGTT) and intraperitoneal pyruvate tolerance test(ip PTT) were performed to evaluate the effects of surgeries on systemic glucose disposal and hepatic gluconeogenesis. The key genes of BA signaling pathway in the duodenal mucosa, including farnesoid X receptor(FXR), small heterodimer partner(SHP), and Takeda G-protein-coupled receptor 5(TGR5) were evaluated by real-time quantitative polymerase chain reaction 8 wk postoperatively. The duodenal SIRT1, AMPK, and phosphorylated AMPK(p-AMPK) levels were evaluated by western blotting. Rat small intestine epithelial IEC-6 cells were treated with GW4064 and INT-777 to verify the effects of BAs on SIRT1 expression in enterocytes.RESULTS The DJB group exhibited body weight and food intake comparable to those of the sham group at all postoperative time points. The FBG level and area under the curve for the OGTT and ip PTT were significantly lower in the DJB group. The DJB group exhibited higher fasting and postprandial serum TBA levels than the sham group at both 2 and 8 wk postoperatively. At 8 wk after surgery, the DJB group showed higher intraluminal TBA concentration, upregulated m RNA expression of FXR and SHP, and elevated protein expression of SIRT1 and p-AMPK in the descending and horizontal segments of the duodenum. Activation of FXR and TGR5 receptors by GW4064 and INT-777 increased the m RNA and protein expression of SIRT1 and promoted the phosphorylation of AMPK in IEC-6 cells.CONCLUSION DJB elevates intraduodenal BA levels and activates the duodenal BA signaling pathway, which may upregulate duodenal SIRT1 and further contribute to improved glucose homeostasis after DJB.
基金supported by grants from the National Natural Science Foundation of China(No.81373007)Fundamental Research Funds for the Central Universities(HUST:No.2016YXMS222).
文摘Objective Epidemiology studies indicate that green tea polyphenols(GTP)perform a protective effect on cardiovascular diseases,but the underlying mechanisms are complex.The present study aimed to investigate the effect of GTP on high-fat diets(HFD)induced-early vascular aging.Methods Six-week young adult Wistar rats were fed with standard chow or HFD in the presence and absence of GTP(200 mg/kg body weight)for 18 weeks.In vitro experiment,human umbilical vascular endothelial cells(HUVECs)were treated with palmitic acid(PA)and GTP.Results The results showed that GTP alleviated the disorganized arterial wall and the increased intima-media thickness induced by HFD.In addition,the vascular oxidative injury was suppressed following GTP treatment.Furthermore,GTP elevated the ratio of LC3-II/LC3-I and suppressed expression of p62/SQSTM1,and restored SIRT3 expression in the aorta of HFD rats.Consistently,in cultured HUVECs,GTP inhibited cell senescence indicated by SA-β-gal and promoted endothelial autophagy compared with the PA treatment group.The activity of SIRT3 was specifically inhibited by 3-TYP,and the protective effect of GTP was consequently abolished.Conclusion The findings indicated that GTP protected against early vascular senescence in young HFD rats via ameliorating oxidative injury and promoting autophagy which was partially regulated by the SIRT3 pathway.
基金This study was supported by the Ministry of Science and Technology[105-2320-B-002-031-MY3,105-2628-B-002-003-MY3].
文摘Excess caloric intake increases the amount of adipose tissue and contributes to metabolic disorders in disrupted metabolic homeostasis.This study aimed to investigate the anti-obesity effects of ginseng and the alternation of gut microbiota composition in high-fat diet(HFD)-induced obesity.The results showed that HFD treatment influenced body weight gain,adipose tissue accumulation and biochemical parameter changes.Compared to the HFD group,ginseng supplementation of HFD-fed mice decreased body weight,adipose tissue mass,total cholesterol(T-CHO)and high-density lipoprotein(HDL)/low-density lipoprotein(LDL)ratio.To analysis the alterations of gut microbiota,ginseng in dietary supplements decreased Firmicutes abundance and increased Bacteroidetes abundance.Taken together,these findings suggest ginseng may modulate the energy storage and alter gut microbiota composition.
